Immuno-genomic landscape of osteosarcoma

Chia Chin Wu, Hannah C. Beird, J. Andrew Livingston, Shailesh Advani, Akash Mitra, Shaolong Cao, Alexandre Reuben, Davis Ingram, Wei Lien Wang, Zhenlin Ju, Cheuk Hong Leung, Heather Lin, Youyun Zheng, Jason Roszik, Wenyi Wang, Shreyaskumar Patel, Robert S. Benjamin, Neeta Somaiah, Anthony P. Conley, Gordon B. MillsPatrick Hwu, Richard Gorlick, Alexander Lazar, Najat C. Daw, Valerae Lewis, P. Andrew Futreal

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Limited clinical activity has been seen in osteosarcoma (OS) patients treated with immune checkpoint inhibitors (ICI). To gain insights into the immunogenic potential of these tumors, we conducted whole genome, RNA, and T-cell receptor sequencing, immunohistochemistry and reverse phase protein array profiling (RPPA) on OS specimens from 48 pediatric and adult patients with primary, relapsed, and metastatic OS. Median immune infiltrate level was lower than in other tumor types where ICI are effective, with concomitant low T-cell receptor clonalities. Neoantigen expression in OS was lacking and significantly associated with high levels of nonsense-mediated decay (NMD). Samples with low immune infiltrate had higher number of deleted genes while those with high immune infiltrate expressed higher levels of adaptive resistance pathways. PARP2 expression levels were significantly negatively associated with the immune infiltrate. Together, these data reveal multiple immunosuppressive features of OS and suggest immunotherapeutic opportunities in OS patients.

Original languageEnglish (US)
Article number1008
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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